Calcilytics as potential novel therapeutic treatments to halt Alzheimer’s disease

Alzheimer’s disease (AD) is the most prevalent form of dementia.1 The common (>95% of cases) slow-developing form of the ailment is known as late-onset AD (LOAD) or sporadic AD (SAD). The rare (<5% of cases), faster-developing form of the disease is early-onset AD (EOAD) or familial AD (FAD), the symptoms of which manifest at an unusually early age (under 60). These patients carry a mutant gene for the β-secretase 1 (BACE1), or more often the presenilin (PSEN1 or PSEN2), components of the γ-secretase complex causing the overproduction of amyloid-β42 oligomers (Aβ42-os).2


SAD affects millions of people in the Western world.3 Its prevalence increases, reaching around 50% by 85 years of age but has been imperceptibly developing for decades with a slow intra-brain accumulation: first of toxic Aβ42-os, and later of hyperphosphorylated Tau protein oligomers (p-Tau-os). These produce micro-ischemic foci, neuroinflammation, synaptic loss, and neuronal death starting within the entorhinal cortex layer II and the hippocampus and subsequently spreading to cognition-linked upper cortical areas. Eventually, SAD emerges clinically with progressive memory failure.4-6

A lot of effort has been invested in trying to stop or reverse the neuronal damage inflicted by SAD. Hitherto, treating human SAD with drugs or otherwise has met with total failure.7,8 In fact, SAD is a complex human disorder that is only partially modelled in rodents, and examining the effect of potential drugs in animal models has had a low predictive power for treatment of SAD patients. To bridge the gap between animal studies and clinical trials, cortical normo-functioning (untransformed) adult human astrocytes (NAHAs) and postnatal human HCN-1A neurons have been used as a preclinical paradigm. This has recently disclosed exciting evidence of a potential treatment for SAD based on the following discoveries…

The rest of this article is restricted to logged-in members. Login or subscribe free to read it.

Send this to a friend